Study to Evaluate the Safety and Efficacy of KITE-439 in HLA-A*02:01+ Adults With Relapsed/Refractory HPV16+ Cancers
Phase 1
Terminated
- Conditions
- Human Papillomavirus (HPV) 16+ Relapsed/Refractory Cancer
- Interventions
- Registration Number
- NCT03912831
- Lead Sponsor
- Gilead Sciences
- Brief Summary
This study has 2 parts: Phase 1A and Phase 1B. The primary objectives of Phase 1A are to evaluate the safety of KITE-439 and to determine a recommended Phase 1B dose. The primary objective of Phase 1B is to estimate the efficacy of KITE-439 in adults who are human leukocyte antigen (HLA)-A\*02:01+ and have relapsed/refractory human papillomavirus (HPV)16+ cancers.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 8
Inclusion Criteria
- Advanced cancer defined as relapsed or refractory disease after at least 1 line of therapy that included systemic chemotherapy and that is not amenable to definitive locoregional therapy
- HPV16+ tumor as confirmed by the central laboratory
- HLA type is HLA-A*02:01+ per local assessment
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Key
Exclusion Criteria
-
Presence of fungal, bacterial, viral, or other infection requiring anti-microbials for management
- Note: Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Kite medical monitor
-
Primary immunodeficiency
-
History of autoimmune disease (eg, Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years prior to enrollment
-
Known history of infection with human immunodeficiency virus (HIV), hepatitis B (HBsAg positive), or hepatitis C (anti-HCV positive). A history of treated hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative polymerase chain reaction (qPCR) and/or nucleic acid testing
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1A: 1 x 10^7 KITE-439 (Cohort 3) Interleukin-2 Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^7 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 3 x 10^7 KITE-439 (Cohort 4) Interleukin-2 Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 3 × 10\^7 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 1 x 10^8 KITE-439 (Cohort 5) Interleukin-2 Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^8 E7 TCR T cells/kg on Day 0 (maximum allowable dose is 5 × 10\^9 E7 TCR T cells) along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 1 x 10^8 KITE-439 (Cohort 6) Interleukin-2 Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^8 E7 TCR T cells/kg on Day 0 (maximum allowable dose is 1 × 10\^10 E7 TCR T cells) along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1B: KITE-439 Interleukin-2 Participants will receive cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, at a dose selected based on Phase 1A along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 1 x 10^6 KITE-439 (Cohort 1) Cyclophosphamide Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, intravenous (IV) infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^6 E7 T-cell receptor (TCR) T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, subcutaneous (SC) injection, once on Days 0 to 6. Phase 1A: 1 x 10^6 KITE-439 (Cohort 1) Interleukin-2 Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, intravenous (IV) infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^6 E7 T-cell receptor (TCR) T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, subcutaneous (SC) injection, once on Days 0 to 6. Phase 1A: 1 x 10^7 KITE-439 (Cohort 3) Fludarabine Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^7 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 1 x 10^6 KITE-439 (Cohort 1) KITE-439 Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, intravenous (IV) infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^6 E7 T-cell receptor (TCR) T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, subcutaneous (SC) injection, once on Days 0 to 6. Phase 1A: 1 x 10^8 KITE-439 (Cohort 6) KITE-439 Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^8 E7 TCR T cells/kg on Day 0 (maximum allowable dose is 1 × 10\^10 E7 TCR T cells) along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 1 x 10^8 KITE-439 (Cohort 5) KITE-439 Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^8 E7 TCR T cells/kg on Day 0 (maximum allowable dose is 5 × 10\^9 E7 TCR T cells) along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 3 x 10^7 KITE-439 (Cohort 4) KITE-439 Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 3 × 10\^7 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 1 x 10^7 KITE-439 (Cohort 3) KITE-439 Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^7 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 3 x 10^6 KITE-439 (Cohort 2) KITE-439 Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 3 × 10\^6 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1B: KITE-439 KITE-439 Participants will receive cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, at a dose selected based on Phase 1A along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 1 x 10^6 KITE-439 (Cohort 1) Fludarabine Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, intravenous (IV) infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^6 E7 T-cell receptor (TCR) T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, subcutaneous (SC) injection, once on Days 0 to 6. Phase 1A: 3 x 10^6 KITE-439 (Cohort 2) Cyclophosphamide Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 3 × 10\^6 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 3 x 10^6 KITE-439 (Cohort 2) Fludarabine Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 3 × 10\^6 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 3 x 10^6 KITE-439 (Cohort 2) Interleukin-2 Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 3 × 10\^6 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 1 x 10^7 KITE-439 (Cohort 3) Cyclophosphamide Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^7 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 3 x 10^7 KITE-439 (Cohort 4) Fludarabine Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 3 × 10\^7 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 3 x 10^7 KITE-439 (Cohort 4) Cyclophosphamide Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 3 × 10\^7 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 1 x 10^8 KITE-439 (Cohort 5) Cyclophosphamide Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^8 E7 TCR T cells/kg on Day 0 (maximum allowable dose is 5 × 10\^9 E7 TCR T cells) along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 1 x 10^8 KITE-439 (Cohort 5) Fludarabine Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^8 E7 TCR T cells/kg on Day 0 (maximum allowable dose is 5 × 10\^9 E7 TCR T cells) along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 1 x 10^8 KITE-439 (Cohort 6) Fludarabine Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^8 E7 TCR T cells/kg on Day 0 (maximum allowable dose is 1 × 10\^10 E7 TCR T cells) along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1A: 1 x 10^8 KITE-439 (Cohort 6) Cyclophosphamide Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^8 E7 TCR T cells/kg on Day 0 (maximum allowable dose is 1 × 10\^10 E7 TCR T cells) along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1B: KITE-439 Fludarabine Participants will receive cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, at a dose selected based on Phase 1A along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. Phase 1B: KITE-439 Cyclophosphamide Participants will receive cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, at a dose selected based on Phase 1A along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6.
- Primary Outcome Measures
Name Time Method Phase 1A: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLTs) First infusion date of KITE-439 up to 21 days A DLT is defined as protocol-defined KITE-439 related Grade 3 events with onset within the first 21 days following KITE-439 infusion and which do not resolve to ≤Grade 2 events within 48 hours, ≥Grade 4 events with onset within the first 21 days following KITE-439 infusion, regardless of duration.
Phase 1B: Objective Response Rate (ORR) Up to 1.4 years ORR was defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as evaluated by modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- Secondary Outcome Measures
Name Time Method Phase 1B: Percentage of Participants Experiencing Adverse Events Up to 1.4 years Phase 1B: Progression-Free Survival (PFS) Up to 1.4 years PFS was defined as the time from the KITE-439 infusion date to the date of disease progression per modified RECIST v1.1 or death from any cause.
Phase 1B: Percentage of Participants With Anti-KITE-439 Antibodies Up to 1.4 years Phase 1B: Overall Survival Up to 1.4 years Overall survival was defined as the time from KITE-439 infusion to the date of death.
Phase 1B: Duration of Response (DOR) Up to 1.4 years For participants who experience an objective response, DOR was defined as the time from the date of their first objective response to the date of disease progression per modified RECIST v1.1 or death from any cause.
Phase 1B: Levels of E7 TCR T Cells Up to 1.4 years Phase 1B: Percentage of Participants With Replication-competent Retrovirus (RCR) Up to 1.4 years
Trial Locations
- Locations (9)
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
City of Hope
🇺🇸Duarte, California, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States